1. Dendritic Cells Coordinate the Development and Homeostasis of Organ-Specific Regulatory T Cells
- Author
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Haochu Huang, Douglas E. Kline, Peter A. Savage, Julian M. Berger, Nicholas D. Socci, Donald J. Vander Griend, Sven Malchow, Saki Nishi, Daniel S. Leventhal, Victoria Lee, Dana C. Gilmore, and Justin Kline
- Subjects
Male ,0301 basic medicine ,Receptors, CCR7 ,Cell type ,CD8 Antigens ,Cellular differentiation ,Immunology ,Antigen presentation ,Receptors, Antigen, T-Cell ,chemical and pharmacologic phenomena ,Biology ,Lymphocyte Activation ,T-Lymphocytes, Regulatory ,Article ,Immune tolerance ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Antigen ,Cell Movement ,Animals ,Immunology and Allergy ,Transcription factor ,Mice, Knockout ,Antigen Presentation ,T-cell receptor ,Prostate ,FOXP3 ,Cell Differentiation ,hemic and immune systems ,Dendritic Cells ,Cell biology ,Mice, Inbred C57BL ,Repressor Proteins ,Basic-Leucine Zipper Transcription Factors ,Self Tolerance ,030104 developmental biology ,Infectious Diseases ,B7-1 Antigen ,B7-2 Antigen ,Transcription Factors ,030215 immunology - Abstract
Although antigen recognition mediated by the T cell receptor (TCR) influences many facets of Foxp3(+) regulatory T (Treg) cell biology, including development and function, the cell types that present antigen to Treg cells in vivo remain largely undefined. By tracking a clonal population of Aire-dependent, prostate-specific Treg cells in mice, we demonstrated an essential role for dendritic cells (DCs) in regulating organ-specific Treg cell biology. We have shown that the thymic development of prostate-specific Treg cells required antigen presentation by DCs. Moreover, Batf3-dependent CD8α(+) DCs were dispensable for the development of this clonotype and had negligible impact on the polyclonal Treg cell repertoire. In the periphery, CCR7-dependent migratory DCs coordinated the activation of organ-specific Treg cells in the prostate-draining lymph nodes. Our results demonstrate that the development and peripheral regulation of organ-specific Treg cells are dependent on antigen presentation by DCs, implicating DCs as key mediators of organ-specific immune tolerance.
- Published
- 2016
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